Design, synthesis and evaluation of cytisinic derivatives for hypoglycemic activity
10.16438/j.0513-4870.2017-1257
- VernacularTitle:金雀花碱衍生物的设计、合成及降糖活性研究
- Author:
Zhi-ting DAI
1
;
Yong ZHANG
1
;
Sheng TANG
1
;
Ying-hong LI
1
;
Wei-jia KONG
1
;
Dan-qing SONG
1
Author Information
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
cytisinic derivatives;
structure-activity relationship;
glucose consumption;
synthesis;
AMPK
- From:
Acta Pharmaceutica Sinica
2018;53(3):416-424
- CountryChina
- Language:Chinese
-
Abstract:
Taking cytosine, an unique natural product alkaloid as the lead, we designed thirty cytisinic derivatives with different types of 12N-substituents, which were synthesized and evaluated for their activity in the regulation of glucose metabolism in vitro. The compounds 3d, 3g and 6h exhibited the potential hypoglycemic activity and compound 3d had a good pharmacokinetics profile. In terms of mechanism of glucose consumption, the compounds 3d and 6h increased cellular glucose consumption. which might be associated with up-regulation of glucose transporter Glut4 expression and activation of AMPK. The results revealed important roles of these new skeleton compounds as potential new drug candidates for control of blood glucose.
